Systems, processes and computer-accessible medium for providing hybrid flourescence and optical coherence tomography imaging

ABSTRACT

Apparatus and method can be provided for obtaining information regarding at least one portion of a biological structure. For example, using a first arrangement, it is possible to generate a first electro-magnetic radiation to be forwarded to the portion and receive, from the portion, a second fluorescent radiation associated with the first electro-magnetic radiation Further, using a second arrangement, it is possible to obtain information associated with the second fluorescent radiation, and generate at least one image of the portion as a function of the second fluorescent radiation. According to an exemplary embodiment of the present invention, the first arrangement can be inserted into at least one lumen, and the image of the portion may be associated with the at least one lumen.

FIELD OF THE INVENTION

The present invention relates generally to medical imaging and, moreparticularly, to apparatus and process for generating fluorescenceimages representative of functional or molecular activity which mayindicate, e.g., a disease in hollow organs using a catheter approach.According to one exemplary embodiment of the present invention, it ispossible to combine fluorescence imaging technique(s) with opticalcoherence tomography technique(s) utilizing certain optical components,and other anatomical imaging techniques can be utilized as well.

BACKGROUND INFORMATION

Fluorescence images can be generated in-vivo for imaging ofphysiological or molecular function in live biological tissues. Oneexemplary technology that has revolutionized the ways tissue and diseaseprocesses can be visualized relates to the use of externallyadministered fluorescence probes with sensitivity and specificity tocertain molecular, cellular or physiological targets. For example, theseagents can provide the ability to visualize events that may be difficultto otherwise detect in conventional imaging modes, and when combinedwith certain detection systems, very high sensitivity or specificity canbe achieved. Conventionally, fluorescent light has been used forhigh-resolution imaging of biological tissue using fluorescencemicroscopy. For example, a fluorescent light can be emitted from atissue in response to an excitation light source transmitting excitationlight into the tissue. The excitation light can excite the emission offluorescent light from fluorochromes within the tissue. When using anear infrared light, higher penetration depths can be achieved incomparison to using light in the visible region, and a significant partof optical tissue imaging may be performed in the near-infrared.

Due to recent advances in light source and detection, optical imagingtechniques have become increasingly important for the diagnosis andmonitoring of disease. Compared with other imaging modalities, opticalimaging can provide molecular, functional and anatomical tissuecharacteristics, originally coming from the interaction of opticalradiation with intrinsic tissue or with chromophores and fluorochromes.Certain different approaches, such as, e.g., confocal imaging,multiphoton imaging, microscopic imaging by intravital microscopy and/ortotal internal reflection fluorescence microscopy can be used forimaging fluorescence in-vivo. However, the prior techniques and systemsmay not be appropriate for three-dimensional or quantitative imaging ofhollow organs, for example, in intra-vascular or gastro-intestinalapplications.

Certain near infrared fluorescence catheter systems have been developedfor the detecting fluorescence distributions from hollow organs such asthe gastrointestinal tract and cardiovascular system. Such systems relypredominantly on surface information from fluorescence reflectanceimaging, but likely lack the ability to provide quantitative orthree-dimensional information. Such information is important toaccurately map the disease, quantify response to therapies, andgeographically localize fluorescence signals within target pathology.

An exemplary application of a catheter-based fluorescence imagingtechnique and systems may be for the detection of atheroscleroticplaques prone to complication (e.g., vulnerable plaques), as it likelyremains a need for subjects at risk of myocardial infarction. Molecularimaging of inflammatory processes in atherosclerosis appears promisingfor detecting high-risk plaques (see, e.g., Jaffer et al. JAMA 2005;JACC 2006; Circulation 2007 in press). Recently, a near infraredfluorescence (NIRF) molecular imaging technique and catheter system havebeen described to detect inflammation in atherosclerosis using afirst-generation intravascular NIRF catheter (see, e.g., Zhu, Jaffer,Ntziachristos et al., J Phys D: Applied Physics 2005). For example, NIRFcatheter 10 can be provided which may detect an augmented proteaseactivity in an inflamed atheroma using a protease-activatable NIRFmolecular imaging agent, and has been tested experimentally in rabbitaortoiliac atherosclerosis in vivo (n=8 rabbits, as shown in FIGS.1(a)-1(d)). This exemplary catheter 10 (e.g., 0.017″ shaft/0.014″ tip)may be provided on the same platform as clinically employed OpticalCoherence Tomography (OCTî) wires. Due to the relatively low absorbanceand autofluorescence in the NIR window, the signal from NIRfluorochromes (e.g., ex/em 750/805 nm) can be detected through bloodduring catheter pullback 20 as shown in FIG. 1(b). In-vivo salineflushing experiments can show different spectroscopic profiles forplaques compared to the normal vessel wall, and histological analysesreveal strong NIRF signal in cathepsin B-rich and macrophage-rich areasof plaques (see, e.g., Jaffer, Ntziachristos et al. American HeartAssociation 2006; Chicago, Ill.). In addition, while one exemplaryendoscopic Optical Coherence Tomography and Fluorescence Spectroscopycatheter arrangement and technique has been described (see, e.g., HaririL P, et. al. Lasers In Surgery and Medicine 38:305-313 (2006)), suchspectroscopic arrangement/technique does not (a) form images offluorochrome distribution, (b) utilize the OCT information to effectuatefluorescence imaging, as well as quantitative or three-dimensionalimages, (c) may not be suitable for intravascular imaging given itslarge size (e.g., 2.0 mm diameter) and (d) does not address the abilityto resolve multiple fluorochromes via multispectral/deconvolutionmethods described herein.

Further, an intravital catheter-based imaging system (e.g., anangioscope) using geometrical normalization has been considered formolecular imaging in mice (Upadhyay et. al. Radiology 245:523-531(2007)). However the geometrical size and other aspects of such systemdid not facilitate its use for intravascular imaging. None of thesystems described above however provide the imaging robustness of orteach on hybrid anatomical molecular imaging for offering a highlyaccurate diagnostic, monitoring or treatment system and importantly forutilizing anatomical information to correct for photon propagationrelated events in tissue and offer quantitative information that isindependent of (a) catheter placement in the hollow organ, b) variationof optical properties that may affect the fluorescence signal andcontrast achieved, and c) variation of the depth of the activity thatcan similarly affect the fluorescence signal and contrast achieved.

OBJECTS AND SUMMARY OF THE INVENTION

It is one exemplary object of the present invention to overcome certaindeficiencies and shortcomings of the prior art systems and techniques(including those described herein above), and provide an exemplarysystem, process and computer accessible medium for generatingfluorescence images representative of functional or molecular activityof e.g., a disease in hollow organs using a catheter. Another exemplaryobject of the present invention it to combine fluorescence imagingtechnique(s) with optical coherence tomography technique(s) utilizingcertain optical components. While the use of the OCT procedures and/orsystems may be a preferred embodiment, other anatomical imagingtechniques can be utilized instead of or together with the OCTprocedures.

According to one exemplary embodiment of the present invention,apparatus and process can be provided for obtaining informationregarding at least one portion of a biological structure. For example,using a first arrangement, it is possible to generate a firstelectro-magnetic radiation to be forwarded to the portion and receive,from the portion, a second fluorescent radiation associated with thefirst electro-magnetic radiation Further, using a second arrangement, itis possible to obtain information associated with the second fluorescentradiation, and generate at least one image of the portion as a functionof the second fluorescent radiation. According to an exemplaryembodiment of the present invention, the first arrangement can beinserted into at least one lumen, and the image of the portion may beassociated with the at least one lumen.

The first arrangement may receive a third radiation which is associatedwith anatomical characteristics of the portion, and the secondarrangement may generate the image as a further function of the thirdradiation. The third radiation can include information associated withthe radiation received from a reference and from the portion. The firstarrangement may include at least one first optical guiding system and atleast one second optical guiding system at least partially surroundingthe first optical guiding system. The third radiation can be propagatedalong the first optical guiding system, and the second fluorescentradiation may be propagated along the second optical guiding system. Thefirst and second optical guiding systems can each include at least oneoptical fiber.

According to another exemplary embodiment of the present invention, thethird radiation can include information associated with acoustical wavereceived from the portion. The second arrangement can generate the imageby combining the second and third radiations. The first arrangement mayreceive a fourth radiation which is at least partially the firstelectro-magnetic radiation that is reflected from the at least oneportion, and the second arrangement can generate the image as a furtherfunction of the fourth radiation. The second arrangement can generatethe image by combining the second, third and fourth radiations.

In still another exemplary embodiment of the present invention, thesecond arrangement may separate the second fluorescent radiation intoparticular energy components, and generate the image as a furtherfunction of the particular energy components. The first arrangement canseparate the second fluorescent radiation into particular componentsassociated with different depths of the at least one portion, and thesecond arrangement may generate the image as a further function of theparticular components. The first arrangement may include a system whichis configured to focus the first radiation into the at the differentdepths.

With respect to still another exemplary embodiment of the presentinvention, the first arrangement may include a first section which isconfigured to generate the first electro-magnetic radiation and a secondsection configured to receive the second fluorescent radiation. Thefirst arrangement can also include a system which is configured to focusthe first radiation into the portion. The second arrangement is furtherconfigured to receive a further image which is associated the thirdradiation, and generate the at least one image using data associate withthe further image. The second arrangement can separate the secondfluorescent radiation into particular energy components, and generatethe image using the data associate with the further image and furtherdata associated with the particular energy components. The firstarrangement may receive a fourth radiation which is at least partially afirst radiation that is reflected from the portion, and the secondarrangement can generate the image based on the data associate with thefurther image, the further data associated with the particular energycomponents and the fourth radiation.

According to a further exemplary embodiment of the present invention,apparatus and process for obtaining information regarding at least firstand second portions of a biological structure can be provided. Usingsuch exemplary apparatus and method, it is possible, using a firstarrangement, to generate a first electro-magnetic radiation and a secondelectro-magnetic radiation to be forwarded to the first portion and asecond portion, respectively, where the first and second portions areadjacent to one another. In addition, it is possible to receive, fromthe first portion with the first arrangement, a third fluorescentradiation associated with the first radiation; and a fourth fluorescentradiation associated with the second radiation. Further, it is possible,with a second arrangement, to obtain the information associated with thethird and fourth fluorescent radiations, and generate at least one imageof the first and second portions as a function of the third and fourthfluorescent radiations such that the at least one image illustrates thefirst and second portions in a continuous manner. The third and fourthfluorescent radiations may be generated by translating and rotating aparticular arrangement.

For example, a first arrangement can include a third arrangementproviding fluid to the first portion and/or the second portion duringthe application of the first and/or second radiations to the firstand/or second portions. The first arrangement can be inserted into atleast one lumen, and the image of the portion may be associated with thelumen.

In addition, according to one exemplary embodiment of the presentinvention, the apparatus and process can be provided via hybrid imaging,e.g., three-dimensional, quantitative fluorescence images of holloworgans by employing concomitant/integrated imaging of the hollowstructure architecture. In another exemplary embodiment of the presentinvention, a common optical path system may be used for some or most ofthe acquisition to facilitate an accurate co-registration, althoughdifferent components are necessary for architectural and fluorescenceimaging. Further, it is possible to appropriately illuminate,synchronize and process the signals in order to obtain accuratefluorescence images. In addition, architectural hollow organ informationmay be incorporated into the fluorescence imaging model to likelyimprove the quantification.

One exemplary embodiment of the system according to the presentinvention may operate on, e.g., (a) approximately 360-degreefluorescence imaging, (2) concomitant structural imaging with integratedOCT (and/or possibly another modality including but not limited toultrasound, MRI, NIR or other spectroscopy, nuclear imaging); and/or (3)depth-resolved and depth and optical property corrected fluorescenceimaging using OCT registration. This exemplary system (e.g., catheter)may be used on humans with a clinical availability of OCT, the longtrack record of NIR fluorochromes in humans (e.g. indocyanine green),planned clinical trials of a protease-activatable and other NIRF imagingagents, and a rapid OCT approach (e.g., optical frequency domain imaging(OFDI) techniques), that may facilitate comprehensive coronary arterialimaging during a saline injection, as opposed to prior prolonged balloonocclusions.

These and other objects, features and advantages of the presentinvention will become apparent upon reading the following detaileddescription of embodiments of the invention, when taken in conjunctionwith the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Further objects, features and advantages of the invention will becomeapparent from the following detailed description taken in conjunctionwith the accompanying figures showing illustrative embodiments of theinvention, in which:

FIG. 1(a) is an exemplary image of a x-ray angiogram demonstrating amodel NIRF intravascular catheter (arrow) placed percutaneously within ahuman coronary-sized vessel in vivo, whereas the catheter has been placedistal to an experimental atherosclerotic plaque in a rabbit iliacartery;

FIG. 1(b) is an exemplary graph of molecular fluorescence signalreflecting inflammation (protease activity) within the experimentalatherosclerotic plaques. The signals are obtained without flushing andthrough blood in vivo during real-time associated with pull-back of thecatheter;

FIG. 1(c) is an exemplary image/photograph of the ex vivo aortoiliacvessels of the experimental rabbit in FIGS. 1a and 1b , whereasatherosclerotic plaque (arrow) is present in a section of a coronarypathway; and

FIG. 1(d) is another exemplary fluorescence reflectance image of thesame anatomical structure demonstrating strong fluorescence signal inthe iliac artery plaques, with the signal corresponding to the increasedin vivo signal detected by the NIRF catheter so as to confirm adetermination of an ability of the intravascular NIRF catheter to detectinflammation in plaques in vivo.

FIG. 2(a) provides a schematic illustration of an embodiment of thecatheter according to the idea of the present invention:

FIG. 2(b) provides a schematic illustration of another embodiment of thecatheter of the present invention.

FIG. 3 is a schematic diagram of yet another embodiment of the presentinvention configured for acquisition and co-registration of fluorescenceand architectural images.

FIG. 4 is a flow-chart illustrating embodiment(s) of a method of dataacquisition and generation of different types of images with anembodiment of the catheter according to the idea of the invention.

Throughout the figures, the same reference numerals and characters,unless otherwise stated, are used to denote like features, elements,components or portions of the illustrated embodiments. Moreover, whilethe present invention will now be described in detail with reference tothe figures, it is done so in connection with the illustrativeembodiments.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENT(S)

Catheter

According to one exemplary embodiment, it is possible to obtainthree-dimensional fluorescence and architectural images of a holloworgan. This can be achieved with an exemplary embodiment of the systemof the present invention as shown in FIGS. 2(a) and 2(b) that can beused as a catheter 200, 200′ which may utilize a rotating fiber 210inside an appropriate catheter sheath. Such exemplary system/catheter200 can be combined with the ability of performing congruent opticalcoherence imaging as shown in FIGS. 2(a) and 2(b), providing twoalternative exemplary implementations. The fiber 210 of the exemplarysystem 200/200′ can be a common fiber that may combine single mode(e.g., for OCT) and multi-mode operations (e.g., for fluorescencedetection).

As shown in FIGS. 2(a) and 2(b), this exemplary system/catheter 200/200′may include a light collection system 220, 220′ for the multimodedetection (e.g., fluorescence collection), an interferometer system 230,230′, an optical system that can appropriately collect and separatesignals for the two modalities and appropriate wave-guiding andfiltering of excitation light at different wavelengths (not shown) asappropriate for architectural and fluorescence measurements. Typicallyarchitectural OCT measurements are performed in the 1200 nm-1500 nmspectral window and fluorescence measurements at the 600 nm-900 nmspectral window, but other spectral windows can by utilized aselaborated in the section “multi-spectral imaging”. Another exemplarycomponent of the system/catheter 200/200′ can include a synchronizationcomponent (not shown) which is configured to synchronize thefluorescence radiation and the information associated with the OCTsignal and/or other imaging system so that the images collected can bemaintained co-registered.

In operation, electro-magnetic radiation can be transmitted from anelectro-magnetic radiation source (e.g., a light source, laser, etc.)via a splitter. The resultant radiation is transmitted through the fiber210/210′ (which may be situated in a multi-clad core 240 and/or afurther core 250), projected through a lens 260 and deflected to impacta sample 270 (e.g., tissue). The signal returning from the sample 260travels back through the lens 260, via the fiber 210/210′. With respectto the exemplary embodiment of FIG. 2(a), the radiation coming from thefiber 210 is transmitted through another lens 280 to be forwarded to theinterferometer 230, which then generates fluorescence and/or OCTinformation/signal. Referring to FIG. 2(b), the fiber 210 can extendpast a sheath, such the fluorescence radiation/signals can be emittedprior to the returning signals being forwarded to the interferometer230′, and thus the fluorenscence signals and the OCT signals may becollected at difference reception locations.

It is also possible to utilize multiple lenses instead of the lens 280shown in FIG. 2(a) or lens 285 shown in FIG. 2(b), with each lensfocusing or collecting fluorescence, excitation and OCT light andinteracting with the interferometer system 230, 230′. As an alternativeand/or in addition, another exemplary embodiment of the system/catheter300 can be provided in which different fibers 310, 320 and/or lenses canbe used, as shown in FIG. 3. Each of the fibers 310, 320 may be providedfor the respective imaging system (e.g., flourescence imaging andarchitectural imaging). In the exemplary embodiment shown in FIG. 3, anarrangement 300 is used for rotating and interfacing the fibers 310, 320other fibers and/or light paths. According to another exemplaryembodiment of the present invention, two independent imaging systems canvisualize substantially the same area of the tissue 270 at any giventime, and/or co-registered in data post-processing.

Exemplary Fluorescence Detection System

An exemplary embodiment of a fluorescence detection system according tothe present invention can include a synchronized photon detector modulecontaining attenuation optics to facilitate a dynamic range operation.This exemplary detection can be detection from a focal point due toappropriate focusing from the optical system, a broader surface areaand/or tissue sectioning detection. An exemplary embodiment of a tissuesectioning detection includes but not limited to a method whereappropriate optics are used to reject light from other areas but an areaof focus inside tissue, for example, a confocal detection ortwo/multi-photon detection. Then, by dynamically changing opticalcomponents, depth dependent measurements can be further achieved.

Exemplary Multi-Spectral System

An exemplary embodiment of the fluorescence detection system can includea multi-spectral detector (e.g., a spectrograph) to achieve amulti-spectral detection. Multi-spectral detection may be useful forrejecting possible auto-fluorescence and for improving quantificationand depth-resolved detection as provided above with respect to theexemplary embodiment of the fluorescence processing method. Suchexemplary process can generate images at multiple wavelengths andextract therefrom an image that may correspond to known spectra ofmultiple utilized fluorochromes that can provide complementaryinformation. In other exemplary embodiments, data and images at certainwavelengths can be utilized to process data obtained in otherwavelengths so as to separate signatures of known wavelengths ofinterest, or to determine fluorescence patterns of biomedical interest.In the simplest exemplary form, the processing operation may include asubtraction operation, and other processing methods utilized inmulti-spectral imaging can be applied. For example, certain exemplarymodels that simultaneously recover spectral signatures and depth can bealso applied.

Illumination

An exemplary illumination can be adapted for use with the fluorochrome,which can be variable. For example, according to one exemplaryembodiment of the present invention, the illumination at a relativenarrow spectral region (e.g., <50 nm) can be used for a fluorochromeexcitation, and can be produced by an appropriately tuned laser source(e.g., having less than 1-5 nm spectral width). Broad beam excitationcan be utilized in parallel to collect optical heterogeneitycharacteristics (e.g., heterogeneous) attenuation from the hollow organwall to provide an independent measurement of hemoglobin distribution,and to provide an improved basis of fluorescence data processing, asdescribed herein. Light of different wavelengths can be channeledthrough the optical system simultaneously, and corresponding signals maybe separated at the output using appropriate spectral separationtechniques, for example the use of filters or spectrographs.

Rotation and Pull Back Mechanism

In an exemplary embodiment of the present invention shown in FIG. 3, theexemplary catheter 300 can utilize (a) a catheter rotation mechanism330, and/or (b) an automated pull-back mechanism to capture holloworgans, e.g., assuming 360-degrees geometries (not shown). The image maybe assembled under a computer/automated control, precisely marking therotation and pull-back operation in physical units (e.g., degrees, cm)to produce a dimensionally accurate image. This exemplary image may berendered using appropriate computer software and procedures usingthree-dimensional rendering techniques and/or two-dimensionalrepresentatives of the three-dimensional image.

I. Exemplary Method

The exemplary embodiments and results thereof according to the presentinvention that can be performed by the exemplary catheter system areshown in FIG. 4. In particular, one exemplary embodiment of the methodaccording to the present invention facilitates a generation ofsemi-quantitative three-dimensional images (procedure 490). Anotherexemplary embodiment of the method is provided to generate quantitativefour-dimensional fluorescence images, which can be co-registered via anoptical coherence tomography technique/procedure (procedure 495). Stillanother exemplary embodiment of the method according to the presentinvention is provided to facilitate a superimposition of raw 360° data(procedure 440). According to a further exemplary embodiment of thepresent invention, it is possible to a superimpose corrected 360° data(procedure 460).

For example, fluorescence data can be collected in procedure 410 andarchitectural data may be collected in procedure 420. The results ofsuch fluorescence data and architectural data collection can beforwarded to procedure 430 for image processing and registration. Theoutput of procedure 430 can be provided such that raw 360° data can besuperimposed in procedure 440. Further output of procedure 430 may beforwarded to procedure 450 for multi-spectral processing of the data.One output of procedure 450 can be used to superimpose corrected 360°data in procedure 460.

In addition, procedure 410 can provide an output for a confocalcollection (procedure 475) which forwards results thereof for confocalprocessing (procedure 480). The output of procedure 480 can be forwardedto procedure 490 to facilitate the generation of semi-quantitativethree-dimensional images Further, procedure 420 (i.e., the architecturaldata collection procedure) may forward an output thereof to a procedurewhich facilitates image segmentation and optical property assignment(procedure 470). Output of procedure 470, along with the output ofprocedure 460 and procedure 480, are forwarded to a procedure forinversion with priors (procedure 485), which then provided an output forthe generation of the quantitative four-dimensional fluorescence images,which can be co-registered via OCT technique/procedure (procedure 495).Provided below is a further description of exemplary procedures 430,450, 480, 485 which can facilitate in the performance of the exemplaryembodiments discussed herein above.

It should be understood by those having ordinary skill in the art thatthe procedures described herein and shown in FIG. 4 may be implementedby a computer which executes software stored in a storage arrangement ofthe computer (e.g., hard drive, RAM, ROM, CD-ROM, etc.) to facilitateits processor so as to perform such steps.

a. Fluorescence Imaging/Co-Registration to Architectural Images (Proc.430)

An exemplary processing method according to one exemplary embodiment ofthe present invention which is shown in FIG. 4 as procedure 435 can beprovided to process the fluorescence information available to produce360-degree fluorescence images. These images may be co-registered withthe OCT images (or images obtained with a modality other than OCT),which may be obtained via system synchronization or image registration,under computer control. When the computer control is implemented, it isalso possible to perform reconstruction and rendering of the resultingimages as three-dimensional structures or as two dimensionalrepresentations. Such exemplary representation can utilize methodologiesfor data normalization previously described, for example, in U.S. PatentApplication Ser. No. 60/634,369.

b. Multi-Spectral Processing (Proc. 450)

In another exemplary data processing procedure as shown in FIG. 4 asprocedure 450, spectral imaging of the data is considered. For example,wavelength dependent differences of the emitted spectra can beattributed to auto-fluorescence or other fluorochrome contributions andto a depth-dependent fluorescence activity. In particular, spectralchanges (e.g., shifts) may be obtained as a function of depth, andmulti-spectral imaging procedure 450 can detect and utilize such data tomore accurately resolve depth. Measurements can be written in a matrixform, as follows:

$\begin{matrix}{\begin{bmatrix}{U_{s}\left( {{\overset{\rightarrow}{r}}_{s\; 1},{\overset{\rightarrow}{r}}_{d\; 1},\lambda_{1}} \right)} \\\vdots \\{U_{s}\left( {{\overset{\rightarrow}{r}}_{s\; 1},{\overset{\rightarrow}{r}}_{d\; 1},\lambda_{z}} \right)} \\\vdots \\{U_{s}\left( {{\overset{\rightarrow}{r}}_{sM},{\overset{\rightarrow}{r}}_{dM},\lambda_{z}} \right)}\end{bmatrix} = {\begin{bmatrix}W_{11}^{\lambda 1} & \cdots & W_{1N}^{\lambda 1} \\\vdots & ⋰ & \vdots \\W_{11}^{\lambda\; z} & \cdots & W_{1N}^{\lambda\; z} \\\vdots & ⋰ & \vdots \\W_{M\; 1}^{\lambda\; z} & \cdots & W_{MN}^{\lambda\; z}\end{bmatrix} \cdot {\begin{bmatrix}{f\left( {\overset{\rightarrow}{r}}_{1} \right)} \\\vdots \\{f\left( {\overset{\rightarrow}{r}}_{N} \right)}\end{bmatrix}.}}} & {{Eq}.\mspace{14mu}(1)}\end{matrix}$The left-most vector of Eq.1 is the measurement vector for each detectorat position {right arrow over (r)}_(d,i), due to a source at position{right arrow over (r)}_(s,i) and for each of z spectral bands acquired.The right-most vector is the vector of unknown fluorescence strengths ineach of the assumed N voxels reconstructed, in which case voxels canextend to a selected depth, generally determined by the maximum depthreached by light in each particular wavelength utilized. Further, themiddle matrix is the weight matrix, which maps the space of unknowns tothe space of measurements. Each of the elements W_(mn) ^(λi) describesthe effect that the fluorochrome at voxel n has on the measurement m,obtained at wavelength λ.

The functions W can be determined analytically or numerically forhomogeneous or heterogeneous optical background. The description of theheterogeneous background can be provided based on information retrievedby the correlative modality (for example OCT) as described herein forthe “a-priori” information. When functions W are calculated for ahomogenous medium, Eq.1 may accurately reconstruct fluorescencebio-distribution in highly heterogeneous media, e.g., when utilizingmeasurements of light attenuation, by recording fluorescence at emissionwavelengths, as well as light attenuation at the same or similarwavelengths as the input light utilized.

Solution of Eq. 1 using algebraic reconstruction techniques can providea preferable inversion performance, in order to retrieve depth andimprove quantification of fluorescence, as described in Ntziachristos V.et. al., Nat. Biotech. 2005. An exemplary embodiment of an inversionmethod that can provide an acceptable performance, (e.g., also due toits relevance in the use of prior information from OCT or othermodality) can be the minimization of a cost function, e.g.,C({right arrow over (x)})=∥{right arrow over (y)}−W{right arrow over(x)}∥ ² +Q({right arrow over (x)}),  (2)where y is the measurement vector U of Eq. 1 and Q({right arrow over(x)}) is a penalty function which is used in the stand alonereconstructions as a regularization function. An exemplaryimplementation of Q({right arrow over (x)}) can then be provided underthe Tikhonov regulation i.e. Q({right arrow over (x)})=λ∥{right arrowover (x)}∥², and the minimization of the problem can be performed usingconjugate gradient methods. This is one exemplary embodiment of themethod according to the present invention, and other exemplary methodsto solve for the problem described for Eq. 1 are within the scope of thepresent invention.

This exemplary procedure can be further implemented and modified byimaging of a (e.g., non-fluorescent) light attenuation providedexternally by the illumination system and captured as described herein.Alternatively or in addition, images of the (e.g., non-fluorescent)light may be also presented as stand-alone to indicate the underlyingoxy- and deoxy-hemoglobin concentration or other tissue chromophores,e.g., also utilizing spectral un-mixing procedure(s).

c. Confocal Processing (Proc. 480)

Exemplary confocal detection procedures can assist with a rejection ofthe scattered light, and may provide more accurate fluorescence imagesfrom a certain depth per scan performed. Combined with depth focusingcapacity, this exemplary procedure may further be used to resolve depth.The overall processing of these images is described in procedures 430and 450 which can include further plotting of the fluorescence ascollected from different depths, using, e.g., computer controls, and afourth dimension may be added in the image of depth (e.g., 360-degreesurface representation, length of the scanned vessel or hollow organ anddepth of vessel or hollow organ wall). Because this exemplary procedure480 may utilize additional collection time, it does not have to besubstantively used, but can be enabled to analyze particular suspiciousareas or the entire vessel at slower acquisition speeds.

d. OCT use as Image Prior (Proc. 485)

Further, the exemplary procedure 485 may utilize the OCT information tobe provided into a fluorescence reconstruction model to, e.g., improvefor the quantification accuracy of the exemplary method and/or impartdepth resolving characteristics. This can be achieved, e.g., byconverting the OCT images to optical maps assuming pre-determinedvalues, and/or guided by the multi-spectral measurement of(non-fluorescent) light, representative of background attenuation. Sincedifferent wavelengths of light propagate at different depths,sufficiently diversified wavelengths (for example, green, red andnear-infrared) can better reveal information of attenuation at differentdepths. This exemplary information may then be incorporated in aregularizer into the inverse problem as an additional term in anexemplary minimization equation:

$\begin{matrix}{\hat{x} = {{\text{arg}{\min\limits_{x}{{Q\left( {{Wx} - u} \right)}}_{2}^{2}}} + {\lambda{{Lx}}_{2}^{2}}}} & (3)\end{matrix}$

The a-priori information can be used to generate the weight matrix W, toform an accurate prediction of a photon propagation (e.g., using atransport-equation based simplification of photon propagation) and/or inthe λ∥Lx∥₂ ² term by appropriately assigning piece-wise regularizationparameters in the L matrix as it corresponds to similarly grouped voxelsin vector x. here in u represented the vector of measurements orprocessed measurements (see Eq. 1). This exemplary procedure can improvethe accuracy and quantification capacity over stand-alone operationabove. Such exemplary procedure may be a post-processing procedure andit generally does not interfere and indeed complements (and enhances)the improvements already achieved by with procedures 450 and 480. Thisexemplary procedure can also utilize OCT image processingprocedures/techniques to differentiate between different structures thatcan be achieved manually, semi-automatically or automatically by imagesegmentation procedures.

The foregoing merely illustrates the principles of the invention.Various modifications and alterations to the described embodiments willbe apparent to those skilled in the art in view of the teachings herein.Indeed, the arrangements, systems and methods according to the exemplaryembodiments of the present invention can be used with any OCT system,OFDI system, Spectral domain OCT (SD-OCT) system, time domain OCT(TD-OCT) system or other imaging systems, and for example with thosedescribed in International Patent Application PCT/US2004/029148, filedSep. 8, 2004, U.S. patent application Ser. No. 11/266,779, filed Nov. 2,2005, and U.S. patent application Ser. No. 10/501,276, filed Jul. 9,2004, the disclosures of which are incorporated by reference herein intheir entireties. It will thus be appreciated that those skilled in theart will be able to devise numerous systems, arrangements and methodswhich, although not explicitly shown or described herein, embody theprinciples of the invention and are thus within the spirit and scope ofthe present invention. In addition, to the extent that the prior artknowledge has not been explicitly incorporated by reference hereinabove, it is explicitly being incorporated herein in its entirety. Allpublications referenced herein above are incorporated herein byreference in their entireties.

What is claimed is:
 1. An apparatus for obtaining information regardingat least one portion of a chosen biological target, comprising: acatheter having proximal and distal ends and an axis and including afirst channel and a second channel, wherein the first and secondchannels together are configured to transmit at least first, second, andthird radiations, wherein said first channel includes a first opticalwaveguide and is configured to transmit through the distal ends towardsthe proximal end, the first radiation that includes one of a mechanicalradiation and an optical radiation including fluorescent radiation, thefirst radiation generated within said biological target in response toabsorption by said target of third radiation transmitted throughcatheter from the proximal end; wherein said second channel includes asecond optical waveguide and is configured to transmit, from saidbiological target through the distal end towards the proximal end, thesecond radiation representing anatomical characteristics of said targetand containing optical-computed-tomography (OCT) information; whereineach of the first and second channels is structured to deflect aradiation transmitted through such channel to cause said radiation totraverse a first portion of such channel along the axis and a secondportion of such channel along a line that is transverse to the axis;wherein said first optical waveguide dimensioned to channel only thefirst radiation and the second optical waveguide is dimensioned tochannel only the second radiation; wherein the catheter is configured tooutcouple said first and second radiations from the first and secondoptical waveguides at respectively corresponding first and secondlocations, wherein the first location is defined at an outer surface ofthe first optical waveguide away from an output facet of the firstoptical waveguide at a proximal end thereof, the second location definedat an output facet of the second optical waveguide at a proximal endthereof, and a detector operably connected with the proximal end toacquire radiation energy and to produce output data representing saidtarget, said output data including a first data portion representing thefirst radiation and a second data portion representing the secondradiation.
 2. The apparatus according to claim 1, wherein the first andsecond optical waveguides extend beyond a sheath of the catheter,wherein the first optical waveguide is configured to emit said firstradiation from an output surface of the first optical waveguide at alocation prior to a proximal end of the first optical waveguide.
 3. Theapparatus according to claim 1, further comprising a programmableprocessor operably connected with said detector, wherein said firstradiation includes incoherent radiation, said second radiation includescoherent radiation, wherein said processor is enabled by program codestored on a tangible non-transitory computer-readable medium to extract,from said output data, data components representing portions of saidfirst radiation at different wavelengths, which portions are receivedfrom different depths of said target, wherein the processor is furtherconfigured to generate first images of said target based on a) said datacomponents and b) optical maps, which optical maps establishcorrespondence between the different depths of the target andwavelengths, and generate second images of said target based on theportion of the output data representing said second radiation, whereinsaid first and second images are spatially co-registered.
 4. Theapparatus according to claim 1, wherein said first radiation includesultrasound.
 5. The apparatus according to claim 1, wherein, inoperation, both the first and second radiations are caused by the thirdradiation transmitted to the target through the catheter.
 6. Theapparatus according to claim 1, wherein the catheter is dimensioned tobe inserted into a lumen of the chosen biological structure.
 7. Theapparatus according to claim 1, wherein the second radiation is producedby said biological target in response to a fourth radiation transmittedthrough a channel of the first and second channels from the proximalend, the fourth radiation being different from the third radiation, eachof the first, second, third and fourth radiations traversing a firstportion of one of the first and second channels along the axis and asecond portion of the one of the first and second channels along a linethat is transverse to the axis.
 8. The apparatus according to claim 1,wherein said first optical waveguide is coaxial and concentric withrespect to said second optical waveguide.
 9. The apparatus according toclaim 1, further comprising a programmable processor operably connectedto the detector and programmed to generate at least one first imagebased on i) the first data portion and ii) the second data portion usedas image prior for the first portion and at least one second image basedon the second data portion.
 10. The apparatus according to claim 9,wherein said processor is programmed to convert the second data portionto an optical map that represents a distribution of an attenuationparameter as a function of depth in said target, from said distribution,to generate a function that represents a correction to the first dataportion, said correction defining contribution of second radiationacquired by the detector from a first depth in said target on secondradiation acquired by the detector from a second depth in said target;to form a corrected first data portion by weighing said first dataportion with the function.